Dean, K.M. et al. Biophys. J. 108, 2807–2815 (2015).

Light-sheet microscopy is a popular tool for biological imaging that offers advantages such as low photodamage, good optical sectioning and high speed. However, owing to out-of-focus light, single-photon light-sheet microscopes face a trade-off between z resolution and the size of the field of view, meaning that only small regions can be imaged with diffraction-limited z resolution. Dean et al. overcome this issue using a new light microscopy setup in which excitation light is swept through the sample along the y axis, yielding a thin strip of in-focus fluorescence surrounded by a blur. So that only the in-focus light is captured, a corresponding subset of pixels in the camera is made active in synchrony with the excitation light. The method yielded isotropic 390-nanometer resolution over a large volume and was used for three-dimensional tracking of clathrin-coated pits.